The overall goal is to understand the genetic basis of, and identify quantitative trait loci for, risk factorsfor[unreadable] cardiovascular disease including LDL density, HDL level, and apoB level, as well as PLTP activity, in families[unreadable] with familial combined hyperlipidemia (FCHL). FCHL is the most common lipid disorder leading to premature[unreadable] vascular disease. Small dense LDL, depressed HDL level, and elevated apoB level are important[unreadable] atherogenic components of the phenotype of FCHL. PLTP activity is an important covariate. Use of four[unreadable] large FCHL families will increase sample homogeneity and joint consideration of covariates, including[unreadable] plasma lipoprotein transfer protein activity, will improve power to detect linkage for these loci. These[unreadable] investigations consider large families with FCHL and evidence of Mendelian segregation of each trait, for[unreadable] whom a 10 cM genomic scan has already been completed, allowing efficient mapping studies of these[unreadable] atherogenic FCHL-related phenotypes. Three loci with significant evidence of linkage were identified for[unreadable] adjusted LDL size (peak particle diameter), using both Iod score and newer Markov chain Monte Carlo[unreadable] (MCMC) methods in analyses of both each family separately and the families combined. Usng these[unreadable] methods for complex traits is expected to result in detection of significant linkage evidence for HDL and[unreadable] apoB level. These will be followed by fine mapping and efforts to identify the underlying genes, beginning[unreadable] with LDL size/density traits. Mapping followed by identification of previously undetected genes for these traits[unreadable] will advance both the basic biology of lipid disorders and the potential to diagnose, prevent, and treat[unreadable] vascular disease.